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Contemporary Review of Injectable Facial Fillers
Abstract
Perhaps the most significant change in facial rejuvenation in the last 10 years has been the introduction of nonsurgical treatments for the relaxation of facial wrinkles and for the restoration of lost volume. Fillers such as paraffin and silicone have been used in the past for volume restoration, but only recently have new fillers been developed whose safety and efficacy have been supported by clinical research. The introduction of hyaluronic acid (HA) fillers in 2003 began the filler revolution and paved the way for development of biostimulatory and permanent materials. There is an abundance of high-level evidence-based studies comparing the HA fillers, calcium hydroxylapatite, and poly(methyl methacrylate) with collagen and other HA formulations, but there is only limited high-level data evaluating poly-L-lactic acid.
... 5 The demand for injectable fillers continues to increase, 6 and new fillers have been developed just recently, whose safety and efficacy are supported by research. 7 There are many types of ideal fillers currently used by cosmetic and medical indication, in routine clinical practice. They can be classified as temporary, semi-permanent or permanent, and according to product composition. ...
... As the PLLA microparticles degrade, the inflammatory reaction responsible for the degradation of the particles promotes the formation of fibrous connective tissue and neocollagenesis, leading to gradual volume replacement. 3,4,7,10 In addition, PLLA increases fibroblast activity and stimulates collagen synthesis. The result is not the effect of the product, but of the host's response to this process. ...
... 15 As a natural skin component, HA has the advantages of not causing rejection, having low immunogenic action, and possessing viscoelastic and hygroscopic properties. 7 These characteristics promote increased skin hydration when HA is applied as a dermal filling, characterized by excellent mechanical properties and moderate durability. 3 In fact, after 30 days of analysis, the present histological investigation showed that HA occasionally was sparsely distributed, and no inflammatory process was observed at any of the time points evaluated, thus emphasizing its favorable biological properties. ...
Purpose
Skin ageing is marked by structural and functional changes in epidermis and dermis, which result clinically in wrinkles, loss of elasticity, and rough-textured appearance. In this context, different dermal fillers have been used to overcome these negative effects associated with skin ageing, such as hyaluronic acid (HA) and poly-L-lactic acid (PLLA). Despite their low immunogenicity, these materials can cause an inflammatory reaction after application.
Materials and Methods
Considering high demand of HA and PLLA as filler material, this study aimed to evaluate their in vitro and in vivo effects. For the in vitro study, human dermal fibroblast cell cultures were supplemented with HA or PLLA for 24, 48, and 72 h. The following parameters were assayed: 1) cell proliferation, 2) cell viability, and 3) quantification of type I collagen by ELISA. For the in vivo study, HA or PLLA was injected in the dermis of Wistar rats and the tissues were collected after 15, 30, and 60 days for histologic evaluation and for quantification of type I collagen by Western blotting. The quantitative data were statistically analyzed using an ANOVA two-way. The significance level was set at 5%.
Results
At 72 h, high cell proliferation was observed for HA compared to control (p<0.05). Cultures exposed to PLLA exhibited a reduction in both cell proliferation and viability compared to control in all time points (p<0.05). Type I collagen expression was greater in cultures exposed to HA or PLLA compared to control (p<0.05). Histologic analysis showed the presence of multinucleated cells only in the PLLA group in all experimental time points. Western blotting analysis revealed high content of type I collagen in HA compared to PLLA (p<0.05).
Conclusion
The present study addresses a potentially unfavorable effect of dermal PLLA filler on the fibroblast phenotype, with possible clinical complications, unlike HA.
... Gli unici filler ad azione temporanea approvati al momento dalla FDA sono l'AI, l'IC e la PLLA (ovvero l'acido poli-L-lattico). Ci sarebbe poi da annoverare il PMMA (acido poli-metil-metacrilato), unico filler permanente attualmente approvato, ma per via dell'irreversibilità delle correzioni da esso apportate, non viene impiegato nella rinoplastica non chirurgica, ergo non spenderemo ulteriori parole su di esso [18]. Prima che ricevesse l'approvazione dalla FDA nell'uso come filler dermatologico, essa era già stata approvata per l'aumento volumetrico delle corde vocali vere, per riparazioni oro-maxillofacciali e come marker radiologico nei tessuti molli [18]. ...
... Ci sarebbe poi da annoverare il PMMA (acido poli-metil-metacrilato), unico filler permanente attualmente approvato, ma per via dell'irreversibilità delle correzioni da esso apportate, non viene impiegato nella rinoplastica non chirurgica, ergo non spenderemo ulteriori parole su di esso [18]. Prima che ricevesse l'approvazione dalla FDA nell'uso come filler dermatologico, essa era già stata approvata per l'aumento volumetrico delle corde vocali vere, per riparazioni oro-maxillofacciali e come marker radiologico nei tessuti molli [18]. ...
... Dopo alcuni mesi, le microsfere verranno poi degradate a ioni calcio e fosfato e quindi escreti dall'organismo [22]. Attualmente l'IC gode dell'approvazione dell'FDA per l'utilizzo come filler dalla funzione volumizzante per le rughe dell'area nasolabiale e in generale come volumizzante per le perdite di sostanza nel terzo medio e terzo inferiore del volto [18]. In particolare, in queste aree si è notato un effetto ottimo nel rimpolpare i solchi commisurali e distendere le rughe a marionetta, le rughe geniene e le labio-mentali [23]. ...
... The patient was uncertain of the name of the website or the filler material. She was unaware if the material was nonpermanent (temporary), semipermanent, or permanent [2]. ...
... (1) Patients with facial dermal filler complications may be initially misdiagnosed as oral cancer. Therefore, their identification is paramount (2) Changes to the UK regulation in 2016 has led to an increased prevalence of facial dermal fillers selfinjected by patients ...
There has been a rise in nonsurgical cosmetic procedures seen within the UK population in the past decade. A change in legislation has placed restrictions on the distribution and provision of such treatments. Therefore, patients may seek alternative methods to bring about a change to their appearance, such as self-injection of a filler. Complications may include oral ulceration, foreign body tissue reaction, and infection due to a lack in sterility during injection. Such presentations may mimic that of oral cancer and can lead to misdiagnoses and undue cost to the National Health Service. This case highlights the common features leading to correct identification of patients self-injecting with facial fillers and discusses the controversy surrounding the economic aspects of their care. We would like to report one such case presenting to our oral and maxillofacial surgical unit.
... 7,8 Hyaluronic acid filler continues to be an increasingly prominent treatment option for perioral rejuvenation. 9 Hyaluronic acid filler injection is routinely performed in the mid to deep dermis to improve the appearance of deep facial wrinkles and folds such as nasolabial folds, perioral rhytids, and prejowl sulci. However, there is limited literature regarding deeper injection of hyaluronic acid in the perioral region to compensate for the muscle atrophy and bony resorption aspects of perioral aging and to address the elongated upper lip. ...
... Hyaluronic acid filler is a popular nonsurgical treatment that is commonly used to improve perioral lines, jowling, and thin, down-turned lips at the soft tissue level. 9 Nevertheless, the use of hyaluronic acid filler injection to combat premaxillary bony deficiency has not been widely pursued or studied. ...
Background
This is the first study to evaluate the effect of premaxillary filler injection on nasal tip projection, upper lip projection, and upper lip vermillion height.
Objective
The primary objective was to analyze the change in nasal tip projection (measured by Goode’s ratio) and the change in upper lip projection (measured by the Z angle) following premaxillary hyaluronic acid injection. A secondary objective was to measure the change in upper lip vermilion height. We hypothesized that treated subjects will show an increase in nasal tip projection, upper lip projection, and upper lip vermillion height.
Methods
Twenty volunteer patients with signs of perioral aging or poor upper lip projection were enrolled in this prospective cohort study and underwent premaxillary hyaluronic acid filler injection between November 2017 and June 2018. Nasal tip projection, upper lip projection, and upper lip vermilion height were assessed for from baseline and post-treatment photographs via measurement of the Goode ratio, Z angle, and lip vermilion height ratio, respectively.
Results
No significant change was noted among pre- and post-treatment Goode ratio measurements (p=0.841). There was an observed significant decrease in Z angle and therefore significant increase in upper lip projection with treatment (p<0.001). Measurement of lip vermilion height ratio demonstrated a trend of increased upper lip vermilion height but without statistical significance (p=0.561).
Conclusions
Our findings showed that premaxillary filler treatment resulted in a significant increase in upper lip projection. Premaxillary filler injection when performed in a safe manner is a valuable treatment option for perioral rejuvenation.
... Also, the Sculptra Ò functions as biostimulatory agent by stimulating the creation and vascularization of collagen [74]. Therefore, the Sculptra Ò was also approved as a cure for nasolabial folds, facial wrinkles, lines and enhancement of contour deficiencies [80]. ...
... Lists of injectable soft tissue fillers by dates of FDA approval (modified by Ref.[80]) ...
Background
Injectable biomaterials have attracted increasing attention for volume restoration and tissue regeneration. The main aim of this review is to discuss the current status of the injectable biomaterials for correction of tissue defects in plastic and reconstructive surgery.
Methods
Requirements of injectable biomaterials, mechanism of in situ gelation, characteristics, and the combinational usage of adipose-derived stem cells (ADSCs) and growth factors were reviewed.
Results
The ideal injectable biomaterials should be biocompatible, non-toxic, easy to use, and cost-effective. Additionally, it should possess adequate mechanical properties and stability. In situ gelation method includes physical, chemical, enzymatic and photo-initiated methods. Natural and synthetic biomaterials carry their pros and cons due to their inherent properties. The combined use of ADSCs and growth factors provides enhanced potential for adipose tissue regeneration.
Conclusions
The usage of injectable biomaterials has been increasing for the tissue restoration and regeneration. The future of incorporating ADSCs and growth factors into the injectable biomaterials is promising.
... This preference arises from its durability, low tissue reactivity, reduced likelihood of causing artifacts on CT scans, and an excellent safety profile in MRI studies, making it a superior choice over stainless steel and cobalt-chromium alloys. [59][60][61] Calcium hydroxyapatite (CaHA), radiance/radiesse It is the most used injectable implant approved by the FDA under the name of "radiance/radiesse" for the correction of nasolabial folds (NLFs), HIV-associated facial lipoatrophy, for perioral, melolabial, nasolabial rhytids, and recently for hand rejuvenation. [62] Furthermore, it has found application in addressing marionette lines, the pre-jowl sulcus, oral commissures, the posterior mandible, and in off-label use-cases such as the temple and malar/submalar areas. ...
Exploring diverse biomaterials and implants in the ear, nose, and throat by understanding adverse effects and post-usage events. Literature was obtained from Scopus, PubMed, Google Scholar, and Web of Science. A comprehensive analysis was conducted on original research studies, case reports, and case series spanning from December 2010 to May 2022. Our analysis underscores that the effectiveness of cochlear implants (CIs) relies on factors such as biocompatibility, anti-inflammatory measures, and fibrosis reduction. Although silicone is employed in otologic applications, allergic reactions leading to CI extrusion are rare. In the context of partial ossicular replacement prostheses or total ossicular replacement prostheses, polyethylene grafts (Teflon) are utilized, and Nitinol-pistons are employed in stapedotomy, with adverse consequences encompassing graft extrusion and residual perforation. Chronic sphenoid sinusitis is linked to the use of Medpor porous polyethylene implants in sellar reconstruction during skull-based surgeries. Injectable collagen preparations in vocal cord paralysis lead to submucosal deposits and resultant dysphonia. Montgomery T-tubes are employed for subglottic stenosis but are associated with granulation tissue formation. Metallic tracheostomy tubes give rise to secondary foreign bodies, and double-lumen tracheostomy tubes are prone to biofilm formation. Despite numerous research studies, there remains a necessity for the refinement of implant designs to mitigate complications and enhance the overall quality of life for patients.
... Implementation of these protocol adjustments resulted in a reduction of complications [9][10][11]. By 2009, PLLA was FDA approved for facial volumization and wrinkles correction [12]. Since then, PLLA has been used extensively as a facial filler, showing long-lasting results, high levels of patient satisfaction, and low percentage of mild adverse events [13,14]. ...
Background
Poly‐l‐lactic acid (PLLA) injectables have gained increasing attention in aesthetic medicine due to their biocompatibility and long‐lasting effects. Although their primary application centers around facial rejuvenation, their potential for off‐label use in other body areas has been investigated, demonstrating promising outcomes in terms of both efficacy and safety.
Aim
This study aims to assess the safety and efficacy of a novel 630 mg PLLA‐based filler (GANA X), in buttocks treatment.
Methods
Six physicians treated 51 patients for buttock aesthetic treatment across six different medical facilities in Italy. A survey was filled by both physicians and patients regarding treatment safety, efficacy, and change in quality of life.
Results
We reported minor or mild adverse events, self‐resolving within the next few days. Both physicians and patients confirmed notable aesthetic improvements following treatment, varying from moderate to significant enhancement. These effects endured throughout follow‐up visits spanning up to 24 months. Patient‐reported outcomes indicated elevated self‐esteem and improved quality of life posttreatment.
Conclusions
The high level of satisfaction reported by both physicians and patients highlights the efficacy and tolerability of GANA X filler for buttocks treatment, encouraging their use and research for off‐label body areas.
... Hence, PDO filler is appropriate for those seeking a gradual enhancement [32]. Additionally, it may provide benefits compared to hyaluronic acid-or CaHA-based fillers because of its enhanced stability and long-lasting outcomes [42]. ...
One of the most notable signs of an aging face is the nasolabial folds (NLFs), which often diminish emotional well-being and self-confidence. To address this concern, many people seek solutions to improve their appearance, often turning to fillers. The ULTRACOL100 device, a tissue restoration material, has been previously investigated and shown to exhibit significant efficacy in both in vitro and in vivo studies. In this research, we aim to explore the safety and effectiveness of the clinical trial of ULTRACOL100 in improving the skin in the NLF area over an 8-week observation period. Male and Female adults with nasolabial folds received two injections of ULTRACOL100, with a 4-week interval between treatments, on one side of their faces. On the other side, they received control materials (REJURAN®, JUVELOOK®, or HYRONT®). The assessment of skin improvement in the nasolabial fold area for each subject took place before and four weeks after each application. Various skin parameters, such as roughness, elasticity, moisture, transparency, trans-epidermal water loss, tone, radiance, skin pore size, and skin density, were measured to evaluate the outcomes. The application of the ULTRACOL100 device significantly reduced the skin roughness, the trans-epidermal water loss, and the skin pore size and increased the skin’s elasticity and internal elasticity, as well as the skin’s moisture, transparency, skin tone, radiance, and density. This study comprehensively investigates the effectiveness and safety of the ULTRACOL100 device, comparing it with three commercial products (REJURAN®, JUVELOOK®, and HYRONT®). The ULTRACOL100 device showed comparable performance in improving the appearance of the NLF area among this study subjects.
... In addition to skin aging, three-dimensional losses are seen in the face, involving bones, muscles, and fat pads that affect the aged appearance. Many dermal llers have been used to minimize these losses, lling in wrinkles and restoring the volume of tissue lost, either due to disease or aging [5]. Soft tissue llers are less invasive with less downtime than traditional surgical interventions[6]. ...
Injectable facial fillers are excellent options for treating facial aging, wrinkles, and contour defects. Both polycaprolactone (PCL) and hyaluronic acid (HA) have been used to restore lost tissue volume and improve facial contour. However, the mechanisms involved in the effect of these biomaterials still need to be fully understood. The present work aims to establish an experimental model to investigate cellular and morphological changes in the skin of Wistar rats in response to HA and PCL to understand the mechanisms associated with these effects. The subcutaneous tissue of the back of Wistar rats was used as a reception area for biomaterials, represented by the commercial products Ellansé®, containing polycaprolactone (PCL) and Juvederm Voluma®, containing hyaluronic acid (HA). Animals were euthanized afetr 30 or 60 days, and skin samples were collected from treated and untreated animals (CONTROL) for histological and immunohistochemical evaluation for IBA-1, TGF-β, and FGF. Analysis of type I and type III collagen deposition, neovascularization, and adipose tissue was performed. On histological examination, HA appeared as an amorphous, basophilic material interspersed with connective tissue bundles. The skin fragments with PCL showed intense cell proliferation, with foreign body giant cells and a higher capillary proliferation than the HA group. More vessels were observed in the HA and PCL groups compared to the CONTROL group. A significant increase in fibroblasts and fibrocytes was observed in skin fragments inoculated with HA and PCL, associated with increased FGF expression. The number of fibroblasts was significantly higher in the PCL group than HA. The PCL group showed higher immunostaining for IBA-1 and TGF-β than the CONTROL and HA groups. Collagen deposition was observed in the treated groups, especially type III collagen in the PCL group, when compared to HA. Our morphological results demonstrated stimulation of fibroblastic activity and active-related tissue regeneration, with increased vascular proliferation and expression of markers related to tissue proliferation, mainly associated with the PCL group. We also observed increased adipose tissue, although further studies are needed to confirm these findings.
... The volume-increasing effect of PDLLA is known to be maintained until 20 weeks after injection [68]. This gives PDLLA an advantage over HA because its volume effect lasts longer and it also stimulates collagen synthesis by modulating immune cells [69,70,88]. ...
Poly-D,L-lactic acid (PDLLA) filler corrects soft tissue volume loss by increasing collagen synthesis in the dermis; however, the mechanism is not fully understood. Adipose-derived stem cells (ASCs) are known to attenuate the decrease in fibroblast collagen synthesis that occurs during aging, and nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) increases ASCs survival by inducing M2 macrophage polarization and IL-10 expression. We evaluated the ability of PDLLA to induce collagen synthesis in fibroblasts by modulating macrophages and ASCs in a H2O2-induced cellular senescence model and aged animal skin. PDLLA increased M2 polarization and NRF2 and IL-10 expression in senescence-induced macrophages. Conditioned media from senescent macrophages treated with PDLLA (PDLLA-CMMΦ) reduced senescence and increased proliferation and expression of transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) 2 in senescence-induced ASCs. Conditioned media from senescent ASCs treated with PDLLA-CMMΦ (PDLLA-CMASCs) increased the expression of collagen 1a1 and collagen 3a1 and reduced the expression of NF-κB and MMP2/3/9 in senescence-induced fibroblasts. Injection of PDLLA in aged animal skin resulted in increased expression of NRF2, IL-10, collagen 1a1, and collagen 3a1 and increased ASCs proliferation in aged animal skin. These results suggest that PDLLA increases collagen synthesis by modulating macrophages to increase NRF2 expression, which stimulates ASCs proliferation and secretion of TGF-β and FGF2. This leads to increased collagen synthesis, which can attenuate aging-induced soft tissue volume loss.
... Nesse sentido o aumento de volume da face vem sendo cada vez mais utilizado através de técnicas de rejuvenescimento facial moderno, principalmente nos casos em que o paciente não quer envolver procedimentos cirúrgicos [26][27][28] . ...
Os procedimentos estéticos, como a harmonização facial, aumentaram significativamente nos últimos anos. O uso de preenchedores com ácido hialurônico, bioestimuladores e fios de PDO são ótimas opções de tratamento para casos de envelhecimento da pele, perda de volume e flacidez. O presente trabalho relata o caso de uma paciente de 50 anos, com perdas volumétricas importantes como olheiras, perda de volume labial e pouca projeção do mento e grau de flacidez moderado. A paciente foi tratada com bioestimulador de hidroxiapatita de cálcio, no terço médio e inferior da face, preenchimento com ácido hialurônico nas olheiras, lábios e mento e fios de PDO espiculado, para maior sustentação da face. Os resultados mostraram melhora dos aspectos da pele com relação à firmeza, sustentação e volume.
... When compared to collagen for the treatment of nasolabial folds, HA not only produces similar cosmetic results with smaller doses but also lasts longer. 2 Nevertheless, some complications may arise with the use of HA dermal llers. Vascular occlusion is the most concerning complication of all, caused either by intravascular injection (arterial or venous), external compression (mostly of the veins), thrombosis or embolization. ...
Facial injections with hyaluronic acid (HA) dermal fillers have become increasingly common. Hyaluronic acid is currently the most frequently used dermal filler. When compared to collagen for the treatment of nasolabial folds, HA not only produces similar cosmetic results with smaller doses but also lasts longer. Our objective was to evaluate the results of 10 patients with vascular complications associated with HA fillers treated with ultrasound-guided injection of hyaluronidase (HYAL) according to the Brazilian Society of Dermatology guidelines. Admission clinical evaluation revealed that the most frequent signs were: livedo reticularis (100% of the patients), hypoesthesia (50%) and local pain (20%). Although 80% of the patients complained of local pain during HYAL injection, none of them persisted with pain after the procedure ended. The total dose of injected HYAL per patient ranged from 300 to 750 IU (mean 500 IU). Post-HYAL treatment Doppler ultrasound showed pervious facial arteries and veins in 100% of the patients.
... If it is used for lip augmentation, it may result in a large number of nodules. erefore, injections in these areas are not recommended [118]. ...
Objective:
This review aims to summarize different kinds of applications of minimally invasive surgery in improving facial aging to provide a comprehensive and accurate introduction on the issue of esthetic treatment of facial skin. Overview. In the twentieth century, facial rejuvenation has become a new beauty trend. Facial cosmetology has entered a period of antiaging and rejuvenation therapies and microplastic surgery. The pursuit of beauty has promoted the development of minimally invasive plastic surgery. This review introduces the possible causes of facial aging and its related topics with a focus on facial injectable drugs, such as botulinum toxin, main filler materials (hyaluronic acid, calcium hydroxyapatite, poly L-lactic acid, collagen, autologous fat, and polymethyl methacrylate), and some current antiwrinkle technologies, such as thread lift and radiofrequency rhytidectomy.
Conclusions:
Despite the difference in mechanisms of action, each technique can address facial aging involving the loss of collagen, displacement and enlargement of fat, and muscle relaxation. Combinations of these treatments can provide patients with reasonable, comprehensive, and personalized treatment plans.
... Bellafill is a bovine collagen filler approved for the treatment of nasolabial folds and moderate to severe facial acne scars, that you can still get today. The industry knew that a better product was needed (Kontis, 2013). ...
One of the most common manifestation in our time, especially among girls, is those procedures on the skin or maintaining or to modify some of the changes in the skin, such as those that come due to aging or any other cosmetic reasons. Fillers and Botox are two of the most popular procedures. Dermal fillers are effective treatments used to soften and reduce wrinkles and deep lines, fill out the cheeks and smooth facial contours. There are four main types of injectable dermal fillers, including fat, collagen, hyaluronic acid, and microsphere-containing carriers of another material such as polymethyl methacrylate (PMMA). So that to understand any type of injection, it is important to look at its history for valuable lessons and for successful progress. Honestly, it is very interesting to see what and where the world gets in the last 40 years of injectable. Today, we will be examining the brief history of dermal fillers from their bovine collagen roots, to the advanced fillers that are available today. In this review, we aimed to show some types of dermal fillers including a variety of its complication in soft tissue. Also, we try to correlate the factor of lifestyle with its variant effects.
... Many injectable dermal fillers have been developed in recent years, most of which contain hyaluronic acid (HA). These fillers are commonly used for wrinkle correction or volumizing, especially in the forehead, nose, nasolabial fold, chin, and infraorbital area [1,2]. ...
Dermal injectables are the most popular material for facial enhancement, including volumizing and wrinkle correction. However, although hyaluronic acid is the most common component of dermal injectables, the character of hyaluronic acid products is quite variable. These materials can be described in terms of their viscoelastic properties using four parameters. In this article, the author would like to describe these properties in detail. Although many physicians consider this material to be convoluted, thoroughly understanding the characteristics of various injectables enables us to tailor procedures accordingly and to enhance the final results.
... PLLA can stimulate collagen production and vascularization in the whole process, which ultimately causes dermal fiber proliferation, acting as a biological stimulant [40]. Therefore, PLLA is also approved as a treatment for nasolabial fold, facial wrinkles, line, and contour enhancement defects [40,41]. ...
Adipose tissue reconstruction is an important technique for soft tissue defects caused by facial plastic surgery and trauma. Adipose tissue reconstruction can be repaired by fat transplantation and biomaterial filling, but there are some problems in fat transplantation, such as second operation and limited resources. The application of advanced artificial biomaterials is a promising strategy. In this paper, injectable biomaterials and three-dimensional (3D) tissue-engineered scaffold materials for adipose tissue reconstruction in plastic surgery are reviewed. Injectable biomaterials include natural biomaterials and artificial biomaterials, which generally have problems such as high absorptivity of fillers, repeated injection, and rejection. In recent years, the technology of new 3D tissue-engineering scaffold materials with adipose-derived stem cells (ADSCs) and porous scaffold as the core has made good progress in fat reconstruction, which is expected to solve the current problem of clinical adipose tissue reconstruction, and various biomaterials preparation technology and transformation research also provide the basis for clinical transformation of fat tissue reconstruction.
... Societal and behavioural norms as well as published literature point out that women seek aesthetic and cosmetic procedures far more than men 4 , specially in the Orient 5 and especially so for plump females in attempts to improve their self image and societal position. Rejuvenation procedures include several interventions, among which are injection procedures in the different layers of the skin 6,7 . Hence, thorough knowledge of the anatomy of the different layers of the skin of the temporal region cannot be overemphasized. ...
Background: skin of the temporal region is a common site for aging marks and hence
rejuvenation procedures. Accurate localization of the layer of the skin to deliver the injected
material is crucial for highly aesthetic outcomes. This study was conducted to evaluate the
structure of the skin of the temporal region using UBM.
Methods: study participants (45 healthy female volunteers) were screened by a specialized
dermatologist and the temporal region was examined. Fitzpatrick skin classification scheme was
applied and the anthropometric measurements (weight and height) were obtained. The UBM
machine (Acutome (Sonomed, USATM)) was used. The captured scans were then examined to
extract the relevant data (thicknesses of the epidermis, dermis and its layers, hypodermis).
Results: the mean(± standard deviation) age of the study participants was 47.8 ± 8.2 years and the
mean(± standard deviation) body mass index (BMI) was 30.6 ± 3.9 Kg/m2. The mean(±Standard
deviation,range,median) of the epidermis, dermis and hypodermis layers of the skin were
0.08(±0.02,0.04–0.13,0.08), 1.28(±0.32,0.69–1.96,1.27) and 0.84(±0.21,0.46–1.73,0.82) mm respectively.
There was a statistically significant positive correlation between the BMI and the thickness of the
hypodermis layer of the skin (p=0.03).
Conclusion: UBM provides valuable information on and measurements of the skin of the temporal
region of the face in females. Skin layers thicknesses do not change significantly with age or with
skin pigmentation. Plumper females have thicker hypodermis in the skin of the temporal region of
the face.
... Thus, considering its traumatic and invasive nature, use of a safer and less invasive technique such as the application of hyaluronic acid gel (HA) can be considered as a suitable alternative for the treatment of deficient IDP and it can replace the conventional invasive methods. 6 Few authors [7][8][9][10][11] have used commercially available HA in treating IDP deficiency which are expensive and not readily available. Therefore, the objective of the current study was to prepare the economically feasible injectable form of HA without crosslinking agent (which is known to cause allergic reaction in commercially available products) in three different concentrations-HA 1%, 2%, and 5% to evaluate its efficacy in the augmentation of IDP. ...
... 28 Another reconstruction mechanism may be that HA fillers replace the decreased natural HA in interdental papillae. [29][30][31] Although HA is sufficiently fluid in texture to be able to fill the volume of the gap in the defect area, it is also rigid enough to prevent soft tissue collapse within the defect. 8 The pyramidal structure supports the three-dimensional (3D) structure of the interdental region. ...
Objective:
The aim of this study was to compare and evaluate the clinical results obtained in the maxilla and mandible by taking digital impressions following application of hyaluronic acid fillers for the reconstruction of multiple papillary losses.
Method and materials:
Evaluation was made of a total of 200 papilla spaces in 20 patients applied with hyaluronic acid filler injection to consecutive papillae regions in both arches symmetrically. The area of the interdental space and the percentage change in the area value over time was calculated separately for each papilla space by taking digital impressions before the application of hyaluronic acid and at 3, 12, and 24 months after the application.
Results:
A significant improvement was determined in the area values of both arches at 3, 12, and 24 months compared to the baseline values. In the percentage change at 24 months, irrespective of whether the mandible or maxilla, the highest filling percentage of all the spaces was between the canine and lateral incisors. When the 24-month filling percentages were compared between the maxillae and mandibles, the most significant difference was between the central teeth.
Conclusion:
The results showed that success was obtained in both arches with hyaluronic acid filler injection applied for reconstruction of multiple papilla losses; because the filling percentages in the maxilla at 3 months and 12 months were greater than those in the mandible, it can be suggested that results can be obtained more quickly and at a higher level in the maxilla.
... Fat injections were introduced as early as the 1890s but by the 1980s, injectable collagen had become the market leader in semipermanent fillers. It offered significant improvements in safety compared with the earlier substrates but was associated with a high incidence of allergy and inflammation [3]. ...
Purpose of review:
The use of dermal filler in the periocular area is increasing - both for functional and aesthetic indications. Hyaluronic acid fillers dominate the market; these treatments offer an alternative to some surgical procedures with the advantage of instant results, minimal healing time and low complication rates. However, success depends on judicious selection of patients, products and procedures to achieve favourable outcomes. This article reviews current understanding of the principal complications in the periocular area and their management.
Recent findings:
Hyaluronic acid is a ubiquitous, biodegradable, nonspecies-specific molecular substrate with limited potential for immunogenic reactions. However, in the periocular area, such products can migrate and last significantly longer than the expected filler lifespan. Contamination or subsequent immune stimulation can trigger delayed-onset inflammatory reactions. Though minor vascular occlusions are not uncommon, cases of blindness secondary to facial filler injections are thought to be rare. Timely enzymatic degradation with injectable hyaluronidase can be effective in the treatment of some such complications. But recent studies demonstrate lack of penetration through arterial walls and optic nerve sheath, casting doubt on the role of retrobulbar hyaluronidase in the management of vision loss because of embolism with hyaluronic acid filler.
Summary:
Hyaluronic acid fillers represent an emerging and important addition to the armamentarium of the oculofacial plastic surgeon with their use in the aesthetic field also expected continue to rise. The oculoplastic facial surgeon, armed with a thorough knowledge of facial anatomy, safe injection planes and the means of minimizing and treating complications is in the best position to lead clinically in the use of this well tolerated and effective treatment modality.
... Knowledge of these viscoelastic properties guides physicians on appropriate product selection based on desired results. 14 The most common descriptor for fillers is elastic modulus (G´). It is used to describe the firmness of a gel and represents the ability of a gel to resist deformation by an applied force. ...
Soft-tissue filler use has grown considerably related to the increasing popularity of minimally invasive cosmetic procedures. Hyaluronic acid products are currently the most utilized soft-tissue fillers. Proper working knowledge of individual products, limitations to use, and anatomic principles can improve outcomes. Prevention is key to minimize complications; however, when present, complications must be managed methodically. Complications are categorized based on the timing of presentation and include early, late, and delayed. Vascular compromise and tissue necrosis are among the most devastating complications seen with filler use. Nodules can be related to an inflammatory or infectious etiology but should be distinguished as treatment varies. Hyaluronidase is mandatory to have available as a reversal agent for hyaluronic acid products and can be used in treatment for many complications and untoward sequela.
... Hyaluronic acid (HA) filler injection has become an established popular treatment option for perioral rejuvenation. 10 The American Society of Plastic Surgery, in fact, reported that over 2 million HA filler procedures were performed in 2017. 11 HA filler injection is routinely performed in the mid-to-deep dermis to improve the appearance of deep facial wrinkles and folds such as nasolabial folds, perioral rhytids, and prejowl sulci. ...
As individuals age, distinct anatomical changes of the bone and soft tissue result in the development of rhytids in the perioral region. Most notably, the oral commissures turn downward, creating the appearance of a perpetual frown and adding years to the facial appearance. The purpose of this article is to review the anatomical changes associated with perioral aging as well as discuss potential treatment options for perioral rejuvenation particularly at the level of the oral commissures. Lastly, this article covers the senior author's technique for improving oral commissures and restoring youthful appearance of the perioral region.
... Since 1997, facial filler use in the United States has increased 356%. 5 Another reason for the exponential increase has been the popularization of fillers and botulinum toxin in social media and news coverage, both locally and internationally. For instance, the average interest level in facial fillers increased by 30% after Kylie Jenner announced using Juvederm (Allergan) lip injections. ...
There has been widespread coverage of cosmetic procedures, particularly facial fillers, as minimally invasive options for facial rejuvenation. The authors' objective was to characterize news media's coverage of facial fillers and its role in shaping public perception of these products over the past decade. Public view plays a significant role in policymaking, assisting patient communication, and addressing preconceived notions. Google News was searched for online news coverage related to “facial fillers” from 2008 to 2017. News articles from various sources were reviewed and analyzed with multiple objectives including complications listed, advantages, disadvantages, physician specialties, overall theme of the articles as positive, negative, or neutral and other parametrics. A chi-square test was used for statistical analysis. Of 426 articles meeting inclusion criteria, international news (20.4%), tabloids (18.8%), online health sites (18.3%), and national news (16.9%) were represented. Of articles containing adequate information, coverage was 44.7% positive, 29.9% neutral, and 26.1% negative with no significant change from 2008 to 2017. In addition, 46.0% of papers discussed complications including vascular injury and blindness associated with fillers, with significant increase by 2017 (p < 0.05). Facial fillers media coverage was overall positive, with broad coverage at both national and international levels. Complications were discussed often, and although vascular injury and vision damage are rare complications of fillers, they were frequently cited, potentially leading the public to believe they occur frequently. There were also significant concerns in the news media about greater regulation of products used as facial fillers, and practitioners administrating them. Altogether, these findings provide a comprehensive overview of patient perception and expectations of an increasingly popular and expanding cosmetic procedure.
... It offers noteworthy advantages over PLLA-based fillers in as far as the results are immediately visible, and over HA-and CaHA-based fillers, thanks to the stability and duration of the results. 42 The efficacy and the safety of this PCL-based stimulator have been demonstrated in clinical trials 19,20,22 and throughout the extensive clinical experience that has been acquired over many years worldwide. Carruthers et al, 17 in their introduction to dermal fillers, mentioned the PCL collagen stimulator and referred to the study of Moers-Carpi and Sherwood, 20 indicating that this product was particularly efficient when used in the NLFs, with no serious adverse effects. ...
Background
The range of fillers currently available for soft-tissue augmentation is constantly expanding. The latest advances in filler technology include collagen biostimulators that exert their esthetic effect by promoting neocollagenesis. One such product is the next-generation collagen biostimulator (Ellansé®) that demonstrates properties as yet unseen in soft-tissue fillers. It is composed of polycaprolactone (PCL) microspheres in an aqueous carboxymethylcellulose gel carrier. Given its specific characteristics and the number of areas that can be treated with this innovative product, experts’ recommendations were deemed necessary and are therefore presented in this paper with a specific focus on the indications, treatment areas and procedures as well as injection techniques.
Methods
A multinational, multidisciplinary group of plastic surgeons and dermatologists convened to develop recommendations with a worldwide perspective. This publication provides information on the specific characteristics of the product and focuses on the recommendations on the injection techniques.
Results
Recommendations on injection techniques are provided for the upper face, mid-face and lower face and zone by zone for each of these areas, as well as hands. Based on the particular anatomy of each area, the focus is on the techniques and devices of injection and the volume and depth of injection. The information is tabulated, and photos are presented for illustration.
Conclusion
These recommendations provide a guideline for physicians who wish to perform safe and efficacious treatment with the PCL collagen stimulator for face and rejuvenation with volume augmentation.
Dear students, future cosmetologists,
The teaching material we present uses data from research and websites on current topics in the field of aesthetics and cosmetology such as anti-aging treatments, skin rejuvenation, body shaping and fat reduction, tattoo removal as well as treatments for slimming and body shaping. These are primarily new insights based on the application of hardware devices used in cosmetology practice around the world. In each separate topic, the indications, the necessary qualifications and permits for the use of the device, the method of dosing, the side effects and all that are based on medical documentation from published professional papers are processed.
Medical science is clearly moving forward, we must follow new knowledge, both in terms of effects and side effects when applying certain cosmetic treatments. As uncommercial as it may seem, medical ethics should be observed when applying these treatments. Guided by the principle of doing no harm, we are moving forward towards the application of ethics on a scientific basis.
Every research offers new dimensions in our practical work, this textbook offers just that, education for medical persons, education for practitioners and facts for education for clients, because not everything presented is always harmless.
Aesthetic dermatology is a growing division of dermatology that aims to improve personal appearance and promote aesthetic rejuvenation. According to the American Society for Dermatologic Surgery (ASDS), over 10.3 million cosmetic treatments were performed by dermatologists in 2019. It is critical that practitioners remain updated on advancements in aesthetic dermatology given the high demand for cosmetic procedures. From the implementation of biotechnology in skincare to advancements in minimally invasive procedures, aesthetic treatments have rapidly diversified, expanding the spectrum of treatments available for patients. This chapter will present these innovations and provide practitioners with an updated review of aesthetic treatments.
The injection of facial fillers and botulinum toxin are the minimally invasive anti-aging procedures most frequently used in doctors’ offices. As with any other injectable procedure, complications are likely to occur even in experienced hands; however, we need to identify them early and handle them appropriately. The purpose of this chapter is to outline the fundamentals of minimally invasive facial rejuvenation procedures.
Background
Injectable poly-D, L-lactic acid (PDLLA), under the brand name of AestheFill (Chaeum Pharma GmbH, Berlin, Germany), is a biocompatible, biodegradable, and biostimulatory product used to correct soft tissue volume loss. Its efficacy and safety have not been fully studied in a large cohort.
Objectives
To evaluate the efficacy and safety of a novel dermal filler injectable poly-D, L-lactic acid.
Methods
This is an evaluator-blinded, multi-centered, randomized controlled trial to compare the efficacy and safety of PDLLA versus hyaluronic acid in the correction of nasolabial fold. Two hundred and sixty patients with moderate to severe nasolabial fold were enrolled and randomized to treatment group (PDLLA) or control group (hyaluronic acid). Each patient received PDLLA or hyaluronic acid injection for nasolabial fold augmentation and followed up for 52 weeks. Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were used to evaluate topical nasolabial fold augmentation and overall improvement, respectively.
Results
At 24 weeks, 67.6% of patients in the PDLLA group had at least 1-grade improvement in WSRS, compared to 60.9% of patients in the control group with at least 1-grade improvement in WSRS (p<0.05). At each visit, PDLLA group showed more improvement from the baseline in WSRS than the control group. PDLLA was safe and well-tolerated with no severe adverse events.
Conclusions
PDLLA shows non-inferior efficacy in correcting nasolabial fold compared to hyaluronic acid.
The use of facial soft tissue fillers is increasing with Hyaluronic acid fillers dominating the market. Any injectable filler may elicit moderate to severe adverse events ranging from nodules to infections and vascular occlusion. As Hyaluronic acid is a ubiquitous, biodegradable, non-species-specific substrate with limited potential for immunogenic reactions, poor aesthetic outcomes are far more common than severe adverse events. This chapter reviews current understanding of the principal complications, recommendations for prevention and their management. Contamination or subsequent immune stimulation can trigger delayed-onset inflammatory reactions. Though minor vascular occlusions are not uncommon, cases of vision loss secondary to facial filler injections are thought to be rare. Timely enzymatic degradation with injectable hyaluronidase can be effective in the treatment of some such complications. However, recent studies demonstrate lack of penetration through the optic nerve sheath, casting doubt on the role of retrobulbar hyaluronidase in the management of vision loss because of embolism with hyaluronic acid filler.
Poly-L-lactin acid (PLLA) has been widely used in the field of bio-medicine. In 2004, as an injectable material, PLLA was approved by the FDA to treat AIDS-related facial atrophy. Since then, several injectable stuffs containing PLLA have been approved for marketing in various countries and regions. Recently, PLLA has often been used to treat facial rejuvenation problems like cutaneous depressions and static wrinkles which always induce unsatisfactory facial expression. This review introduces the physicochemical properties, regeneration stimulating mechanism, applications in aesthetics and injectable comorbidity of PLLA.
Facial aesthetic procedures have become increasingly popular and complex, making knowledge of facial anatomy crucial for achieving desired outcomes without complications. Some of the most common procedures include blepharoplasty, bichectomy, face-lifts, facial implants, thread lifting, and fillers. Blepharoplasty and bichectomy are surgical procedures that respectively aim to restore youthful contours to the periorbita and create a slimmer lower face by removing Bichat fat from the maxillofacial region. Facial implants are used for aesthetic augmentation of the skeletal structure and restoration of facial contour by using biomaterials or autogenous bone grafts. Face-lift surgeries involve incisions and removal of excess skin, and thread lifts involve less invasive procedures performed by inserting threads beneath the skin, with the aim to lift the skin and thus reduce wrinkles and sagging. Fillers improve wrinkles and loss of facial volume, with biologic types made from animal, human, or bacterial sources (such as hyaluronic acid), while synthetic fillers include substances such as paraffin, silicone, calcium hydroxyapatite, polymethylmethacrylate microspheres, polyacrylamide hydrogel, hydroxyethyl-ethyl methacrylate, and poly-l-lactic acid. Synthetic fillers can be classified as rapidly resorbable (<12 months), slowly resorbable (<24 months), or permanent. Imaging modalities such as US, CT, and MRI can help identify and analyze each type of facial aesthetic procedure or filler, as well as their possible complications such as foreign-body granuloma, noninflammatory nodule, late intermittent persistent edema, filler migration, infection, or complications after removal of the buccal fat pad. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center The online slide presentation from the RSNA Annual Meeting is available for this article.
Injectable fillers based on hyaluronic acid are now frequently used to correct tissue volume loss when facial rejuvenation is sought. The way in which these commercially available HA fillers are manufactured has direct implications for the properties of the gel and the clinical applications of these products. These properties can be described using the science of rheology, which describes the flow and deformation of matter, allowing researchers to understand how these fillers act under mechanical stress, either at the time of injection or after implantation of the gel. It is important to note that the mechanical forces exerted on each anatomical region of the face vary in intensity and frequency, causing the filler to deform in different ways. The aim of this study was to review the literature on the rheological properties of hyaluronic acid gels and to emphasize the importance of knowing these properties when selecting fillers, so that harmonizing professionals can achieve the desired results.
Soft tissue fillers have gained tremendous popularity as a minimally invasive intervention for restoring volume loss and facial symmetry due to chronological aging, disease, and trauma [1]. The use of filler for facial reconstruction dates back the 1830s when the first injectable agent, paraffin was introduced followed by autologous fat in the 1890s. It was not until 1981, when Zyderm®, a bovine collagen filler, became the first Food and Drug Administration (FDA) approved agent for soft tissue reconstruction [2, 3]. Since then, various agents have been developed. In 2003, the FDA approved Restylane®, a product made from hyaluronic acid (HA). Shortly after, the market for dermal fillers experienced rapid growth with over 2.5 million injectable procedures performed in the United States in 2019 alone [4].
In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems associated with cosmetic ingredients, products, and procedures, and regulations for eye cosmetic use. In addition, a systematic review that critically appraises randomized controlled trial evidence concerning the ocular effects of eyelash growth products is included. The findings of this systematic review highlight the evidence gaps and indicate future directions for research to focus on ocular surface outcomes associated with eyelash growth products.
Purpose
The aim of this study was to investigate the performance and the reversibility of different classes of Hyaluronic Acid (HA) dermal fillers. We analysed 4 HA based fillers, belonging to 3 different chemical classes of products, commonly used in the field of wrinkles correction: linear HA 8 mg/mL (Viscoderm 0.8), thermically stabilized hybrid complexes of high and low molecular weight HA molecules at a concentration of 32 mg/mL and 45 mg/mL respectively (Profhilo and Profhilo Structura) and cross-linked HA 25 mg/mL (Aliaxin GP).
Methods
The products were tested by a well-established animal model. The generated implants were analyzed through High-Frequency Ultrasound technology. Then, reversibility of the treatment was evaluated by enzymatic degradation kinetics studies, characterised by a combined approach of Carbazole assay and HP-SEC/TDA method.
Results
Implants generated by linear HA 8 mg/mL remained detectable by ultrasound acquisition for 4 weeks, whereas those generated by injection of HA hybrid complex 32 mg/mL were detectable for 10 weeks. HA hybrid complex 45 mg/mL and cross-linked HA 25 mg/mL were detectable for 29 and at least 33 weeks, respectively. Enzymatic degradation kinetics studies demonstrated that the HA content in HA hybrid complex 45 mg/mL was almost completely depolymerized and homogeneous after 3 h of treatment. For cross-linked HA 25 mg/mL, 24 h of incubation are needed to obtain the same degree of depolymerization.
Conclusion
The study confirmed the ability of the experimental model to predict the behaviour of HA based dermal fillers in vivo and showed the innovative aspects of HA hybrid complex 45 mg/mL, that combines the high-safety profile, in terms of reversibility of the treatment, of the linear HA-based products with the durability of a high degree cross-linked gels, paving the way to the chance to be used for a wide range of applications in the field of aesthetic medicine.
Topical cosmetic medications, cosmeceuticals, and minimally invasive cosmetic procedures play an important role in dermatologic practice. Advances have led to a tremendous expansion in the repertoire of nonsurgical cosmetic treatments. Adverse skin reactions to cosmetics include irritant contact dermatitis, allergic contact dermatitis, phototoxic dermatitis, contact urticaria, and foreign body reactions. The clinician should be aware of these potential skin reactions and seek to identify the causative agents and other contributing factors. In the clinical setting, substances that have irritant properties are used to treat acne, hyperpigmentation, and sun‐damaged skin. Preservative allergy is a common cause of skin care product allergy. Preservatives are commonly implicated in allergy to ophthalmic preparations. A thorough history of occupational and environmental exposures is necessary to ascertain potential sources of allergic and irritant contact dermatoses. Treatment is based on identifying the offending agent and subsequent avoidance.
Background
One of the most challenging areas for facial rejuvenation is the lower eyelid. Apart from the protruding orbital fat causing lower lid bags, a discrete entity called the “tear trough deformity” is distinguishable in this area.
Aim
The objective of this study is to compare and evaluate the standard technique of tear trough deformity correction with the lateral injection technique using a high G prime filler to establish a guideline for the safe and effective correction of tear trough deformity.
Methods
A prospective, double-blind, study was carried out from Dec 2017 to 2019 including 30 participants in the age range of 35–60 years. The participants were divided into two groups of 15 patients each. In group A patients, conventional technique with a low G Prime filler was used, whereas in group B, lateral injection technique with a high G Prime filler was used.
Results
Marked improvement was seen in appearance and skin quality on both the sides in all the patients. As compared to our technique (lateral injections) where a mean of 0.5 ml of filler was used to lift the cheek and reduce the tear trough, the standard technique (Mauricio de Maio's 3-point tear trough reshape technique) required a mean of 1.2 ml of filler for the same. Post-procedure complications including bruising and Tyndall effect were much higher (statistically significant) using the standard medial technique for the correction tear trough.
Conclusion
Aesthetically satisfying results for the tear trough correction are possible, without actually injecting the tear trough directly, based on the knowledge of the underlying anatomy.
Purpose
To evaluate the stability of interdental papilla filling using hyaluronic acid (HA) to treat black triangles in esthetic regions.
Methods
The protocol was registered in PROSPERO. Six databases (PubMed, Scopus, Embase, Lilacs, SciELO, and Web of Science) were used as primary search sources, and OpenGrey and OpenThesis were used to capture the “gray literature.” Only before‐after studies were included. The JBI Checklist assessed the risk of bias. Only four studies met the inclusion criteria and were considered for the analyses. The studies were published from 2010 to 2016. All studies presented a low risk of bias. Considering the studies do not have control groups, a weighted average by sample size was calculated to obtain a general estimate of the percentage of papillary filling after 6 months and the number of HA applications.
Results
The studies showed the percentage of papillary reconstruction after 6 months of application, the weighted average by sample size was 77.41% (SD = 20.68), with an average number of applications of 3.17 (SD = 0.31).
Conclusion
The application of HA may be used to repair anesthetic defects in the papilla.
Clinical significance
Interdental papilla reconstruction with injectable HA is an option of nonsurgical treatment for interdental papilla deficiencies. However, there is still concern about the quality of the evidence available, considering that studies with different experimental designs can produce contradictory results. Moreover, further understanding is required on the stability of tissue gain promoted by HA in black triangles.
This chapter serves as a review of lip anatomy, facial analysis with regard to the lips, and treatments for cosmesis. The focus is on the lips in relation to the rest of the face. Minimally invasive and surgical treatments for aesthetic lip procedures are discussed including augmentation and reduction cheiloplasty and treatments for the aging lip.
Biomaterial is defined as a substance other than a drug, which is developed as a whole or part of a complex system, that interacts with the living organisms, and functions for therapeutic or diagnostic purposes. They are widely used in clinics and surgery applications to repair the damaged tissue. Orthopedics diseases, cardiovascular diseases, general and reconstructive surgery procedures dominate the category of disciplines in medicine, where biomaterials are occasionally used. Besides, biomaterials have been widely used in dental procedures, ocular diseases, urological diseases, and wound healing therapies. The term biocompatibility, which defines the ability of a material to perform its function in a specific application with an acceptable host response, has been the cornerstone of investigations in biomaterial researches. It refers to the interaction between biomaterials and living systems, related with an acceptable harm to the organism. In other words, biocompatibility reflects a set of characteristics to use a material safely in a living organism. Briefly, there are three major biological responses that need to be considered for biocompatibility assessment of a biomaterial including inflammation, wound healing, and immunological reactions and/or immunity. Biocompatibility assessment involves various methods including complex in vitro and in vivo experiments, standardized by various organizations such as American Society for Testing and Materials, the British Standards Institute, the International Standards Institute, and the Food and Drug Agency.
Injectable fillers have become a vital part of cosmetology. A wide variety of injectable fillers are developed for either correction of facial wrinkles and folds or facial contouring. As the most popular filler products, polymeric injectable fillers represent a class of the most common implantable medical devices. This review is intended to not only present current filler products, but also share perspectives of future trends, development processes, and regulatory considerations for the next generation of fillers. First, currently approved polymeric injectable fillers are described in detail. Second, future trends of polymeric injectable fillers are discussed. Fillers based on the emerging technologies in tissue engineering and regenerative medicine with stimuli‐responsive or tunable properties, as well as device/drug combination products, are promising candidates. Third, fillers for cosmetology are different from traditionally recognized medical devices. As a result, the target population of such fillers is different from that of other implantable devices, leading to different user needs that impact their development processes. Last, product applications, regulatory requirements, device evaluation, characteristics, and difficulties for regulating filler products for minimally invasive cosmetology are reviewed. Both regulatory science and scientific supervision are needed for polymeric injectable fillers which are facing great opportunities as well as challenges. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48515.
Hyaluronidases are enzymes that degrade hyaluronic acid, which constitutes an essential part of the extracellular matrix. Initially discovered in bacteria, hyaluronidases are known to be widely distributed in nature and have been found in many classes including insects, snakes, fish and mammals. In the human, six different hyaluronidases, HYAL1-4, HYAL-P1 and PH-20, have been identified. PH-20 exerts the strongest biologic activity, is found in high concentrations in the testicles and can be localized on the head and the acrosome of human spermatozoa. Today, animal-derived bovine or ovine testicular hyaluronidases as well as synthetic hyaluronidases are clinically applied as adjuncts to increase the bioavailability of drugs, for the therapy of extravasations, or for the management of complications associated with the aesthetic injection of hyaluronic acid-based fillers. Further applications in the fields of surgery, aesthetic medicine, immunology, oncology, and many others can be expected for years to come. Here, we give an overview over the molecular and cellular mode of action of hyaluronidase and the hyaluronic acid metabolism, as well as over current and potential future clinical applications of hyaluronidase.
Background
Numerous fillers are increasingly used for augmentation of volume loss and relaxation of facial wrinkles. Collagen stimulators are the latest next‐generation dermal fillers that can induce neocollagenesis. To investigate biophysical characteristics, safety, and efficacy of newly developed polydioxanone (PDO) filler in comparison with poly‐l lactic acid (PLLA) and polycaprolactone (PCL) fillers.
Methods
In vitro assay, morphology of particles, and rheological property of fillers were measured. A total of 24 female hairless mice (SKH1‐Hrhr) were randomly divided into three groups and injected with PDO, PLLA, or PCL fillers. Durability of fillers was assessed at 0, 3 days, and 1, 4, 8, 12 weeks after injection using folliscope and PRIMOS. To determine biocompatibility and neocollagenesis, histologic evaluation was performed at 1, 4, 8, and 12 weeks after injection. Efficacy was also evaluated based on skin surface roughness changes using PRIMOS in a hairless mouse photoaging model.
Results
In the particle morphology test, PDO microspheres had an irregular surface and were spherical and uniformly sized. PDO filler demonstrated similar neocollagenesis and inflammatory response to other collagen stimulators. PDO filler showed better biodegradability than PLLA and PCL fillers. In the hairless mouse photoaging model, there was a statistically significant decrease in skin surface roughness after PDO filler injection.
Conclusions
Our data suggest that newly developed collagen stimulating PDO filler might be a safe and effective option for correction of volume loss and rejuvenation of photoaging skin.
Sound knowledge of the rheology of hyaluronic acids is fundamental for facial rejuvenation procedures. Hyaluronic acid implants are subjected to complex mechanical forces within the facial tissues that vary depending on the anatomical region. Analysis of these forces is important to establish the rheological specifications of hyaluronic acid implants in each specific zone. This approach will optimize the correction of age‐related loss of volume, since the filler will be chosen as a function of the mechanics of the anatomical zone, with the objective to respect facial dynamics.
Dermal fillers are highly favored around the globe as minimally invasive or nonsurgical procedures. Imatinib mesylate is the first-line treatment for patients diagnosed with chronic myeloid leukemia. However, some studies describe that imatinib mesylate may increase the tendency of skin fragility which can lead to easy bruising and hyperpigmentation after invasive skin procedures. Yet, to our knowledge, no studies have described any successful dermal filler injection performed on patients who are under imatinib mesylate treatment. Hence, we present a case successfully treated with hyaluronic acid filler injection on a patient under imatinib mesylate treatment. We carefully propose that hyaluronic acid filler can be an effective means of rejuvenation and cosmetic enhancement for those under imatinib mesylate treatment.
Background:
Small-particle hyaluronic acid filler is approved for lip augmentation and correction of perioral rhytides. Treatment with this product may improve facial aesthetics, projected first impression, and self-perception of mood.
Objective:
To determine the effect of perioral rejuvenation with hyaluronic acid on patient perception of mood and projected first impression.
Materials and methods:
Seventeen subjects underwent perioral rejuvenation treatment with small-particle hyaluronic acid filler. Each subject underwent photography and completed 2 surveys measuring self-perception of mood before treatment and after achieving an optimal cosmetic result. Aesthetic improvement with treatment was assessed using the Global Aesthetic Improvement Scale and the Oral Commissure Severity and Perioral Line Severity scales. Seventeen hundred blinded evaluators rated pre-treatment and post-treatment photographs of the subjects using a First Impressions Questionnaire.
Results:
Perioral filler treatment significantly improved pre-treatment and post-treatment scores for happiness within the Happiness Measures Scale. This treatment was found to significantly improve projected first impression across all categories.
Conclusion:
Small-particle hyaluronic acid filler treatment for perioral rejuvenation is an effective method for improving physical appearance as well as first impressions. Larger studies are necessary to verify whether perioral rejuvenation with hyaluronic acid offers enhanced self-perception of mood.
Collagen injection has been used as dermal filler in plastic and cosmetic surgery. A technetium Tc methylene diphosphonate bone scintigraphy was performed in a 47-year-old woman as part of the breast cancer evaluation. The images showed intense methylene diphosphonate activity on both sides of the frontal head, where she received collagen injection 1 year prior. The activity was visualized again in all 3 follow-up bone scans over the subsequent 3 years.
An increasing number of injectable filler materials for facial wrinkles and folds points to the need for objective measurements of their effectiveness. Patient satisfaction is the goal, but proof of the value of a particular product requires objective measurement. A wrinkle assessment scale was developed as a simple tool for use by plastic surgeons, dermatologists, and aesthetic surgeons who want to assess the changes resulting from injecting filler materials in their patients. By correlating the grade of the wrinkle in the reference photographs with the wrinkle in a patient's face, a classification of 0 to 5 is assigned. Reliability of the scale was assessed by "live" judgment of 76 wrinkles by nine observers. The same rating was given to 92.7 percent of all wrinkles. In a second trial, photographs from 130 wrinkles were presented to eight observers who rated 89.4 percent of all wrinkles equally. A significant correlation of 87 percent was found between subjective ratings and objective wrinkle depth measured by profilometry on 40 silicone impressions. Manufacturers, monitors of clinical trials, health authorities, and most important, patients will benefit from objective data on current and new injectable materials.
Most of the biologic filler materials that increase the thickness of the corium in a wrinkle line are phagocytosed within a certain time. Therefore, a lasting effect can only be achieved with nonresorbable synthetic substances. Artefill consists of 20 volume percent microspheres of polymethyl-methacrylate and 80 volume percent of bovine collagen. Beneath the crease, the microspheres with their exceptional surface smoothness stimulate fibroblasts to encapsulate each individual one of the 6-million microspheres contained in 1 mL of Artefill. Collagen is merely a carrier substance that prevents the microspheres from agglomerating during tissue ingrowth. The 20 volume percent of microspheres in Artefill provides the scaffold for the 80% volume of connective tissue deposition, a complete replacement of the injected collagen. The filler material beneath a crease acts like a splint and prevents the possibility of its further folding, thereby allowing the diminished thickness of the corium in a crease to recover. This recovery process is well known even in older patients with facial paralysis or after a stroke, whose facial wrinkles and furrows on the paralyzed side disappear over time.
Repeat treatments of nonpermanent dermal fillers are used in the long-term treatment of wrinkles and folds and to volumize. OBJECTIVE To determine the safety and effectiveness of a nonanimal-sourced hyaluronic acid (HA) (which uses a cohesive polydensified matrix (CPM) technology [CPMHA]) for the treatment of nasolabial folds (NLFs) during an 18-month open-label extension trial.
Ninety-five of 118 subjects continued with this optional open-label extension of a split-face, double-blind trial. All subjects received CPMHA in both NLFs at 24 weeks after treatment in this study and were assessed at weeks 32, 48, 72, and 96. Touch-ups were allowed for optimal correction. Safety was assessed according to reported adverse events (AEs) and serum antibody measurement.
At all four post-week 24 time points, the severity of the NLFs showed a decrease from baseline on the Wrinkle Severity Rating Scale. The effects persisted in the majority (∼80%) of subjects without repeat treatment for at least one interval of 48 weeks. The study filler was well tolerated, with only one related AE (injection site bruising) reported. Little potential for immunogenic reactions was identified.
This CPMHA is a well-tolerated and effective treatment for at least 48 weeks in the majority of subjects for the correction of moderate to severe NLFs with repeat injections given over an 18-month period.
This pilot study compared a monophasic hyaluronic acid dermal filler with a biphasic filler for the correction of nasolabial folds.
Participant- and assessor-blinded, randomized clinical trial involving participants with moderate to severe nasolabial folds. Split-face design comparing a monophase hyaluronic acid (HA) filler (mono-HA) with a biphasic HA filler (bi-HA). Injection with touch-up after 1 month. Wrinkle improvement was measured before and after injection and after 1, 2, 4, and 7 months, using the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale as outcome criteria. An optional treatment was offered at the end of the study, with participants allowed to choose one of the products.
Evaluation of efficacy and safety of both products.
Both products showed immediate, good results after injection and touch-up and demonstrated good durability over time. Participant preference for optional treatment at the end of the study favoured mono-HA. Both products were well tolerated, without serious adverse events.
The effect after injection of mono-HA and bi-HA is generally comparable, although there was a trend in favor of mono-HA. Materials and funding for this study were provided by Teoxane, Geneva, Switzerland.
The purpose of this article is to discuss current techniques used with poly-l-lactic acid to safely and effectively address changes observed in the aging face. Several important points deserve mention. First, this unique agent is not a filler but a stimulator of the host's own collagen, which then acts to volumize tissue in a gradual, progressive, and predictable manner. The technical differences between the use of biostimulatory agents and replacement fillers are simple and straightforward, but are critically important to the safe and successful use of these products and will be reviewed in detail. Second, in addition to gains in technical insights that have improved our understanding of how to use the product to best advantage, where to use the product to best advantage in facial filling has also improved with ever-evolving insights into the changes observed in the aging face. Finally, it is important to recognize that a patient's final outcome, and the amount of product and work it will take to get there, is a reflection of the quality of tissues with which they start. This is, of course, an issue of patient selection and not product selection.
Hyaluronic acid (HA) gels have been used as filler material in the aesthetic field. Although the native HA molecule is without specificity of species and organs, synthetic cross-linked gels have differences in chemical composition and three-dimensional structure. Different technologies are employed in cross-linking, and the products have varying rheological properties.
To determine whether the gels with differing chemical composition have differing histologic behavior when injected into human skin to determine if the histology changes after 14 days of implantation.
Human volunteers consented to having controlled placement of HA intradermally into forearm or buttock skin. The trials were conducted in a single clinic in association with the Hôpitaux Universitaires de Genève, Geneva, Switzerland. The biopsies were taken immediately after implantation of the product and at day 14. Standard paraffin sections were prepared and stained with hematoxylin and eosin and Alcian blue and examined by an independent pathologist.
Results show that each type of HA has a predictable histologic behavior in the skin. Biphasic gel has demonstrated deposition in big pools, often deep in the reticular dermis. The pools compress the collagen fibers. The papillary dermis and superficial reticular dermis are free of HA. Monophasic monodensified gels show large pools of hyaluronans throughout all the thickness of the reticular dermis. This material breaks up the collagen fibers of most of the dermal plane. The papillary dermis is free of exogenous hyaluronans. Monophasic polydensified cohesive gel penetrates into the dermis in a diffuse, evenly distributed manner, except in the papillary dermis, which remains free of exogenous material.
The different types of cross-linked HA have different behaviors in the dermis immediately after their injection. The patterns are consistent between patients and are predictable. These histologic patterns do not change when biopsies are examined at 2 weeks.
Juvéderm™ VOLUMA™ (Voluma) is a new injectable, long-lasting, resorbable hyaluronic acid filler. It restores facial volume, resulting in a more youthful appearance.
To evaluate current in-market perceptions of the aesthetic result and use of Voluma.
Men and women >30 years who had received Restylane SubQ™ (Restylane) <2 years previously, now requiring re-treatment and who consented to Voluma treatment were included.
Eighty-four patients (mean age 51 years, 88% women) were recruited. The mean total volume of Voluma injected was 2.73 mL/patient. This included treatment to both sides of the face, specifically in the malar and chin areas or both (mean 1.36 mL each to the right and left sides of the face). Seventy-five percent of injectors found Voluma fairly/very easy to inject and 84.5% found it easy to sculpt/massage. Most patients (98%) and physicians (98%) rated the aesthetic effect of Voluma as improved. Injectors rated Voluma as better than previous Restylane use in 69.1% of patients (P < 0.001), and preference for Voluma was expressed in 61% of patients (P < 0.001). Ninety-nine percent of injectors would recommend Voluma to colleagues and patients (100%); 96.4% of patients would recommend it to friends. Treatment was well tolerated.
Voluma is easy to use, sculpt, and massage. Physicians and patients rated the cosmetic effects highly, and both groups reported a preference for Voluma in those patients previously treated with Restylane.
The aim of this prospective, rater-blind, randomized, intra-individual, 4-week study was to compare the effectiveness and safety of two hyaluronic acid dermal fillers, Belotero® Basic (monophasic) and Restylane® (biphasic), for correction of nasolabial folds (NLF). Twenty subjects with bilateral, symmetrical NLF were randomized to receive a single injection of Belotero® Basic and Restylane® in a split-face design. The primary endpoint measured intra-individual differences of treatment effects in mean depth and evenness of the NLF target area relative to its edges, from baseline to Week 4, as evaluated by the Phase-shift Rapid In-vivo Measurement of Skin (PRIMOS) system. Assessments were undertaken at Visit 2 (baseline) and Visit 3 (study endpoint). Treatment with Belotero® Basic resulted in a significantly greater improvement in evenness compared with Restylane® at Week 4 (mean intra-individual difference between treatments in PRIMOS measurement: -37.6 μm; 95% CI: -65.4; -9.9). Subject-rated secondary endpoints demonstrated numerical differences in favour of Belotero® Basic when compared with Restylane®. Both dermal fillers were equally well tolerated, as 85% (Belotero® Basic group) and 80% (Restylane® group) rated the tolerability of both treatments as "good" to "very good".
Calcium hydroxylapatite (CaHA) has been administered after nerve block injection of anesthetic agents.
This prospective, randomized, split-face, single-blind study (50 subjects) assessed the pain reduction, safety, and effectiveness of premixing CaHA with 2% lidocaine for the treatment of nasolabial folds (NLFs).
Subjects were randomized to receive treatment with CaHA alone in one NLF (control) and with CaHA premixed with lidocaine in the other NLF (treatment). Subjects completed pain assessments using a validated visual analog scale at specified time points immediately after injection, 1 hour after injection, and 1 month later. Subjects also indicated relative pain experience and preference assessments. Investigators completed aesthetic assessments at 2 weeks and 1 month. Subjects and investigators recorded adverse events.
Subjects reported statistically significantly less pain in the treatment fold than in the control fold and expressed unanimous preference for the treatment injection over the control. Aesthetic results were essentially equivalent for both treatments.
Investigators concluded that CaHA premixed with lidocaine results in significant pain reduction during dermal filler injection while maintaining the aesthetic improvement of CaHA without lidocaine and demonstrating comparable local transient adverse events for treatment and control. BioForm Medical (San Mateo, CA) provided the soft tissue filler, lidocaine, and other necessary supplies used in this study. All authors are members of the Bioform Medical Education Faculty.
Pain during and after implantation of dermal gel fillers is a consistent complaint of patients undergoing soft tissue augmentation. Reduction of pain during injection would increase patient comfort and improve the overall patient experience.
To evaluate pain at the injection site during and after the injection of Prevelle SILK or Captique and to evaluate outcomes after 2 weeks.
In a patient-blinded, prospective, randomized, split-face design trial, a non-animal-derived hyaluronic acid based filler formulated with lidocaine (Prevelle SILK) was injected in one nasolabial fold (NLF), and the same filler without lidocaine (Captique) was injected in the contralateral NLF of 45 enrolled patients. Injection site pain was measured using a visual analogue scale at injection (time 0) and 15, 30, 45, and 60 minutes after injection. Patients were asked to return for an evaluation after 2 weeks and to complete a self-assessment questionnaire during the follow-up visit.
There was more than 50% less pain associated with the dermal gel with lidocaine than with the same filler without lidocaine at all time points (p<.05). The greatest difference in pain was recorded at the time of injection, and then the effect gradually declined over the 60-minute period. Both fillers were well tolerated, and there was no difference in outcome after 2 weeks.
Addition of lidocaine to a filler resulted in significantly less pain associated with the procedure without compromising outcomes.
To assess the safety and effectiveness of hyaluronic acid (HA) fillers in skin of color.
Two prospective studies followed up subjects with Fitzpatrick skin phototypes of IV, V, or VI for 24 weeks after dermal filler injections. In a double-blind, randomized study, subjects were injected with one of three high concentration (24 mg/mL) HA fillers (Juvéderm Ultra, Ultra Plus, and 30) in one nasolabial fold and Zyplast collagen in the other. In an open-label, randomized study, subjects received one of three low concentration (5.5 mg/mL) HA fillers (Hylaform, Hylaform Plus, and Captique) in both nasolabial folds.
A total of 160 subjects (a subset of 439 study subjects) were randomized and treated with one of the three high concentration fillers, and 119 subjects were randomized and treated with one of the three low concentration fillers. For subjects treated with the high concentration fillers there were no occurrences of hypersensitivity or hypertrophic scarring, and no increased incidence of hyperpigmentation or hypopigmentation in non-Caucasian vs. Caucasian subjects. For subjects treated with the low concentration fillers there were no occurrences of keloid formation, hypertrophic scarring, hypopigmentation, hypersensitivity, and three instances of mild hyperpigmentation. For all of the fillers the majority of subjects maintained >/=1 point improvement in nasolabial fold severity scores through 24 weeks.
All of the HA fillers were well tolerated in individuals with skin of color and demonstrated effectiveness throughout the 24 week period. Furthermore, the fillers provided smooth, natural-looking wrinkle correction in darker skin types.
Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin.
This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin.
This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit.
No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded.
People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population.
Injectable calcium hydroxylapatite (Radiesse) received FDA approval in 2006 for the correction of facial lipoatrophy and moderate to severe facial wrinkles. This product consists of microspheres of a synthetic bone suspended in a methylcellulose gel matrix. Because the product is thicker than the hyaluronic acids, it is used for the correction of moderate to severe wrinkles, such as deep nasolabial folds. It is also used "off-label" to treat multiple areas of the face, nose, and hands. Radiesse is injected into the subdermal plane, and correction lasts approximately 1 year after injection.
Over the past decade, the popularity of nonsurgical cosmetic procedures has increased exponentially. Last year, according to the American Society of Aesthetic Plastic Surgery, more than 5 million procedures were performed using cosmetic injectables such as botulinum toxin and dermal filling agents. According to the society's recent statistics, more than 85% of all dermal filler procedures occurred with a hyaluronic acid derivative.These numbers are expected to rise in the future as there is currently no other class of filling agent that rivals the popularity of hyaluronic acid. The popularity of hyaluronic acid specifically stems from its effectiveness, ease of administration, and safety profile.
In an attempt to maintain a youthful appearance or to reconstruct facial deformities, physicians have greeted new technologies with excitement. In the late 1800 s, shortly after the invention of the syringe, chemical agents were used for facial augmentation. Unfortunately, history has taught us that new technologies must be used with care, because complications can occur, sometimes many years after initial treatment. The first injectable filling agent was paraffin, whose use was abandoned after complications of migration, embolization, and granuloma formation were described. More recently, silicone use was banned by the U.S. Food and Drug Administration (FDA) because of similar complications. In 1981, bovine collagen was the first agent to be approved by the FDA for cosmetic injection. Since its approval, dozens of injectable filling agents have been developed, and many are already FDA approved for cosmetic use. This article will review the highlights of the evolution of facial filling agents.
This split-face, single-blind study compared the comfort and ease of injection of a new hyaluronic acid facial filler containing pre-incorporated lidocaine (Juvederm ULTRA 3) versus the established hyaluronic acid facial filler Restylane-Perlane. A total of 126 individuals were treated with both products, randomly assigned to the right or left naso-labial fold. Injector assessment-indicated mean injection pain, pain of massaging the injected area and post-injection discomfort (based on a scale of 0=no pain to 10=extreme pain) were 2.1, 0.9 and 0.4 for Juvederm ULTRA 3, and 4.1, 3.3 and 1.7 for Restylane-Perlane, respectively (p<0.0001). Patient assessment of the same parameters were 2.8, 1.3 and 0.4 for Juvederm ULTRA 3, and 4.9, 3.6 and 1.8 for Restylane-Perlane (p<0.0001). Injectors indicated that 92% of Juvederm ULTRA 3 injections were 'very easy', compared with 21% for Restylane-Perlane. Post-treatment smoothness was comparable, but 95% of individuals preferred Juvederm ULTRA 3 for overall injection comfort. A total of 95% of individuals indicated that Juvederm ULTRA 3 was a more comfortable and gentle experience.
Injectable poly-l-lactic acid (PLLA) has been used to correct age- or disease-related facial volume deficits.
This single-center, retrospective survey evaluated PLLA for cosmetic use.
A questionnaire was mailed to 281 patients treated with PLLA 6 months or more previously. PLLA was reconstituted 4 hours or more before injection with 5 mL of sterile water plus 1 mL of 1% xylocaine added before injection.
Two hundred twenty-one patients responded (210 female; average age 54.3; average treatments 3.3 per patient); the majority had received facial injections. Transient side effects included bruising, swelling, and discomfort. After treatment (1-6 months), 14/41 patients developed Grade 1 papules or nodules (slightly palpable, nonvisible; clinically nonrelevant; all resolved spontaneously), 15/41 developed Grade 2 papules or nodules (palpable, slightly visible; clinically nonrelevant; all resolved spontaneously), and 12/41 developed Grade 3 nodules (easily palpable, obviously visible [9 perioral; 3 periorbital or temple]; 5 resolved spontaneously; 7 were treated [5 intralesional corticosteroids; 2 surgery]).
Patients treated with PLLA experienced duration of improvement of up to 24 months. Maximum improvement took several treatment sessions. Nodules occurred in perioral and periorbital regions, so incidence is reduced by avoiding these areas.
Nonanimal stabilized hyaluronic acid (NASHA) offers longer-lasting correction than many other injectable products and is associated with low risk of immunogenic and hypersensitivity reactions. A new large-particle stabilized hyaluronic acid-based gel has been developed to restore facial volume and define facial contours.
This study was conducted to assess the long-term efficacy and safety of a large-particle stabilized hyaluronic acid-based gel in patients seeking facial contouring.
Fifty-seven adult patients seeking esthetic cheek or chin augmentation or both received subcutaneous or supraperiosteal injections or both of large-particle stabilized hyaluronic acid-based gel (20 mg/mL). Efficacy was assessed subjectively using the Global Aesthetic Improvement Scale at intervals up to 12 months after treatment.
After treatment, patients and investigators independently considered treatment sites to be at least somewhat improved in 91% and 96% (6 months), 68% and 77% (9 months), and 58% and 52% (12 months) of cases, respectively. Patient- and investigator-assessed treatment response rates (the proportion of patients showing at least moderate improvement) were 72% and 81% (6 months), 42% and 40% (9 months), and 21% and 15% (12 months), respectively. Most commonly reported adverse events were local injection-site reactions, skin induration, and implant mobility.
This large-particle stabilized hyaluronic acid-based gel is well tolerated and provides relatively long-lasting esthetic correction of the cheeks and chin after subcutaneous or supraperiosteal injection.
Most HIV-positive patients receiving highly active antiretroviral therapy develop facial lipoatrophy soon after commencing treatment. Attempts to correct lipoatrophy through autologous fat transfer or the use of temporary, semipermanent, or permanent fillers have achieved some benefits, but either do not have lasting effects, do not treat some areas effectively, or have other disadvantages.
The purpose of this article is to outline the treatment principles for use of poly-L-lactic acid (PLLA) in HIV-associated facial lipoatrophy since its emergence in 1999 and review the relevant literature, with particular emphasis on investigations of the incidence of subcutaneous papule formation after PLLA treatment.
The principles of treating facial lipoatrophy with PLLA, including product preparation, patient preparation, and injection technique, are reviewed. Two case studies and results are presented as typical examples of treatment and results. A literature discussion focuses on changes in the incidence of papule formation after PLLA treatment.
In the representative cases presented, 2 white men in their forties with facial lipoatrophy who had been HIV-positive for more than 10 years received 2 vials of PLLA in each of 5 treatments spaced 4 weeks apart. Results are shown 4 weeks after the final treatment. No papules were reported in the 12-month follow-up period.
Early investigations of PLLA for the treatment of HIV-associated facial lipoatrophy reported a significantly high incidence of subcutaneous papule formation. As experience with PLLA has increased, the incidence of papule formation has dropped dramatically. The proper dilution, adequate hydration time, proper placement of the product, sufficient intervals between treatments, and posttreatment massage all have contributed to this decrease.
To assess effectiveness of intradermal injections of autologous fibroblasts for the treatment of facial rhytids and dermal depressions.
Six-month prospective pilot study. Photographs and silicone molds were taken of a prominent rhytid or dermal depression from each patient prior to treatment and at 6 months after treatment.
Specialty clinic in academic medical center.
Ten adults (age range, 24-69 years) who each exhibited a prominent rhytid or depressed facial scar.
A 3-mm postauricular skin biopsy specimen from each participant was sent to Isolagen Technologies, Inc, laboratories, where a fibroblast cell line was developed. Three injection sessions were performed at 2-week intervals; target areas were the study site as well as behind the ear.
Subjective improvement scores were obtained by each patient and 2 clinicians at every follow-up visit. Skin surface topographical features were evaluated with optical profilometry by comparing silicone molds before and after injection. Histological analysis was performed on a biopsy specimen of the postauricular injection site.
Nine of 10 patients noted a 60% to 100% improvement with the treatment; clinicians made similar observations. Size reduction of 10% up to 85% of the study site was demonstrated by optical profilometry for every patient. Microscopically, there was evidence of increased thickness and density of dermal-layer collagen.
Intradermal injection of autologous fibroblasts may be an effective treatment option for facial rhytids and depressed scars.
Bovine collagen is extensively used for facial soft tissue augmentation but provides only temporary correction and can cause hypersensitivity reactions. Hyaluronic acid derivatives potentially offer improved longevity of correction and a reduced risk of immunogenicity and hypersensitivity.
To compare the efficacy and safety of nonanimal stabilized hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) with that of bovine collagen (Zyplast) for treatment of nasolabial folds.
One hundred thirty-eight patients with prominent nasolabial folds were randomized to treatment with hyaluronic acid gel and bovine collagen on contralateral sides of the face. Treatments were repeated at 2-week intervals, as required, to achieve "optimal cosmetic result" (baseline). Outcomes were evaluated by a blinded investigator at 2, 4, and 6 months after baseline.
Less injection volume was required for "optimal cosmetic result" with hyaluronic acid gel than with bovine collagen, and patients and investigators judged hyaluronic acid gel to be more effective in maintaining cosmetic correction. The investigator-based Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale assessments at 6 months after baseline indicated that hyaluronic acid gel was superior in 56.9% and 62.0% of patients, respectively, whereas bovine collagen was superior in 9.5% and 8.0% of patients, respectively. The frequency, intensity, and duration of local injection-site reactions were similar for the two products.
Nonanimal stabilized hyaluronic acid provides a more durable aesthetic improvement than bovine collagen and is well tolerated.
Bovine collagen is widely used as a dermal filler for facial soft-tissue augmentation, but it provides only temporary cosmetic improvement. Nonanimal stabilized hyaluronic acid has reduced potential for immunogenicity and hypersensitivity and may provide a more durable aesthetic result. Sixty-eight patients with prominent nasolabial folds were randomized to intradermal treatment with nonanimal stabilized hyaluronic acid gel (Perlane) and bovine collagen (Zyplast) on contralateral sides of the face. On achievement of "optimal cosmetic result" (baseline), patients were followed up for 6 months; bilateral retreatment with Perlane was offered at 6 or 9 months after baseline. Responses were evaluated at 2, 4, 6, 9, and 12 months after baseline. Investigator-based and patient-based ratings indicated that Perlane was more effective than Zyplast in maintaining cosmetic correction. According to investigator-based Wrinkle Severity Rating Scale assessments at 6 and 9 months after baseline, Perlane was superior in 50.0 percent and 48.8 percent of patients, respectively, whereas Zyplast was superior in 10.3 percent and 14.0 percent of patients, respectively (p < 0.0004). Investigator-based Global Aesthetic Improvement Scale assessment at 9 months after baseline indicated that Perlane was superior in 48.8 percent of patients, whereas Zyplast was superior in 14.0 percent of patients (p = 0.0025). "Optimal cosmetic result" was achieved with a smaller volume of Perlane than Zyplast (mean, 1.2 ml versus 2.1 ml). Local injection-site reactions (redness, swelling, pruritus, and induration) were less frequent with Perlane than with Zyplast. Delayed-onset reactions were rare and did not reoccur after Perlane retreatment. Perlane has acceptable long-term safety and offers a longer-lasting aesthetic improvement than Zyplast.
Polylactic acid (PLA, New-Fill; Medifill, London, UK and Dermic Labs, a division of Eventis, Strasbourg, France) injections into the deep dermis increase fibroblast numbers and collagen production. The substance is widely used in medical applications including cosmetic procedures.
HIV-positive individuals with facial lipoatrophy (based on physician assessment) were randomized to immediate (weeks 0, 2 and 4) or delayed (weeks 12, 14 and 16) PLA given as three bilateral injections 2 weeks apart into the deep dermis overlying the buccal fat pad. Assessments included facial ultrasound, visual analogue scales, the Hospital Anxiety and Depression Scale (HADS) and assessment using photographs at weeks 0, 12 and 24.
All 30 patients completed 24 weeks of treatment. The median age of the patients was 41 years, with a mean of 80 months of nucleoside reverse transcriptase inhibitor (NRTI) therapy and a mean of 44 months of prior protease inhibitor (PI) therapy. The median CD4 count was 428-460 cells/microL, with 47% of patients in the immediate-treatment group and 93% of patients in the delayed-treatment groups with <50 HIV-1 RNA copies/mL at baseline. No differences in immunological, virological, biochemical, haematological or metabolic parameters emerged during the study. Injections were well tolerated with only two adverse events (cellulitis and bruising) recorded, one of which delayed treatment by 1 week. There were no discontinuations. Patient visual analogue assessments, photographic assessments, and anxiety and depression scores improved with treatment. At week 12, immediate-treatment patients had significantly better visual analogue scores (7 vs. 1, P<0.001) and lower anxiety scores (6 vs. 9, P=0.056) than delayed-treatment patients. Benefits on visual analogue and HADS scores persisted until week 24.
PLA injections led to improvements in patient self-perception, anxiety and depression scores in individuals with facial lipoatrophy. Adverse events were uncommon. The benefits of PLA persisted for at least 18 weeks beyond the last injection.
ArteFill, the successor product to Artecoll, is an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, which offers long-lasting and probably permanent augmentation of wrinkles and skin contour deformities. The pivotal U.S. Food and Drug Administration study consisted of 251 subjects at eight centers in the United States who received injections of ArteFill or bovine collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial folds, radial upper lip lines, and corners of the mouth. The efficacy data generated by masked observers using a photographic Facial Fold Assessment Scale demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p < 0.001) in the nasolabial folds. In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant wrinkle correction. A subgroup of 69 patients who received ArteFill were recalled 4 to 5 years later. Five patients reported six late adverse events that occurred from 2 to 5 years after the initial injection; four of the adverse events were mild cases of lumpiness and two were severe. The total number of late adverse events was six of 272 (2.2 percent) wrinkles injected. Among the 272 wrinkles evaluated at 5 years, two events (0.7 percent) in one patient were rated as severe (a nodular, minimally inflammatory to noninflammatory reaction in both nasolabial folds). Investigator Facial Fold Assessment ratings at 4 to 5 years were improved from baseline by 1.67 points (p < 0.001).
Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen.
The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects.
This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection.
Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12-month follow-up, live fibroblast-treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported.
Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection.
Allison Gelfer, Alastair Carruthers, MD, Jean Carruthers, MD, Frances Jang, MD, and Steven C. Bernstein, MD, FRCPC, have indicated no significant interest with commercial supporters.
A novel soft tissue filler composed of polymethylmethacrylate (PMMA) microspheres suspended in a collagen gel matrix containing 0.3% lidocaine (ArteFill, Artes Medical, Inc.) was recently approved by the Food and Drug Administration for the correction of nasolabial folds. A randomized, multicenter, controlled pivotal trial performed in the United States established the safety and efficacy of this medical device throughout a 12-month study period.
The objective was to substantiate the long-term 5-year safety and efficacy of this novel soft tissue PMMA filler.
Attempts were made to contact all subjects treated with the PMMA filler that were enrolled in the original pivotal study. Safety was assessed by standard adverse event reporting methods. Efficacy was determined using a validated six-point facial fold assessment photometric grading scale using blinded observers' assessment of standardized photographs.
Subjects (n=119) demonstrated significant improvement in nasolabial folds comparing baseline (before any treatment) to 5 years after their last treatment (p<.001). Notably, subjects also demonstrated continued improvement between 6 months after their last treatment and Year 5 (p=.002). No serious unanticipated device-related adverse events were reported.
This PMMA filler is the first soft tissue filler to demonstrate continued improvement and persistence of correction over a 5-year period posttreatment.
In this study, we examined Radiesse (calcium hydroxylapatite; CaHA), Juvederm 24 (hyaluronic acid; HA-1A), Juvederm 24HV (HA-1B), and Perlane (HA-2) for patient satisfaction, likelihood to return, immediate efficacy, and duration of correction.
This multicenter, blinded, randomized study compares patient satisfaction variables, efficacy, and durability of CaHA gel and HA for correction of nasolabial folds (NLFs) through 12 months after 4-month touch-up.
A total of 205 randomized patients received either CaHA gel or HA for NLF treatment at initial visit and 4-month touch-up. Patients returned at 4, 8, and 12 months after the second injection for evaluation. Surveys measured patient satisfaction; effectiveness measures included the Global Aesthetic Improvement Scale (GAIS).
More CaHA gel patients were satisfied or extremely satisfied than each HA tested. At 8 months, significantly more CaHA gel-treated NLFs were improved on the GAIS than any HA. The volumes of CaHA gel and three HA materials injected through 4 months were 2.2, 2.9, 4.8, and 2.9 mL, respectively (p<.005). No serious adverse events were observed.
In this controlled study, CaHA gel ranked highest in patient satisfaction and likelihood to return. The material was more effective and longer lasting than each HA in maintaining NLF augmentation.
Each soft tissue filler product has its own unique profile in terms of adverse events. In this large-scale study, we investigated the safety profile of Radiesse, an injectable calcium hydroxylapatite (CaHA) implant, in treatment of nasolabial folds and other areas of the face. We also investigated the efficacy in a subset of the larger patient group.
After obtaining informed consent from the subjects, researchers injected CaHA at two treatment centers into 113 patients (100 women and 13 men, ranging in age from 26 to 78 years) for a variety of facial aesthetic applications over a period of 47 months. Seventy-five patients had a single injection session; 38 had multiple sessions. Most patients (102) received 1.0 mL of CaHA per session; 12 received 2.0 mL per session. Typically, CaHA was administered with a 27-gauge 0.5- or 1 1/4-in. needle.
Safety. Of 113 patients, only 7 reported minor adverse events that were short-term and resolved within 1 month: transient ecchymosis (3), nongranulatomous submucosal nodules of the lip (2), and inflammation and edema (2). Efficacy. Efficacy ratings were performed for a subset of patients (n=41). On a scale of 1 to 5 (1=unsatisfactory; 5=excellent), the mean patient evaluation score for look and feel of the implant was 4.6; the mean physician scores for the look and feel of the implant were 4.5 and 4.6, respectively. During the 6-month follow-up visit, patients' mean ratings of the look and feel of the implant were 4.8 and 4.9, respectively. The physician's mean ratings for the look and feel of the implant were 4.5 and 4.9, respectively.
In our study, CaHA performed well, with a favorable safety profile, high patient satisfaction (90% of patients reported very good or excellent results), and good durability. We are especially pleased with the low incidence of adverse events coupled with the favorable responses from the patients themselves due to longevity of correction.
Fillers continue to proliferate in dermatology. Rigorous clinical trials can help determine the advantages and disadvantages of these products as they come to market.
This randomized, split-face, controlled study compared the efficacy, safety, durability, and volumes of calcium hydroxylapatite (CaHA) versus nonanimal-stabilized hyaluronic acid (NASHA) in nasolabial folds.
Sixty patients were enrolled at two medical clinics in Europe (Summer 2005). Patients received two injections 3 months apart. Patients returned at 6, 9, and 12 months for a blinded evaluation, using accepted aesthetic rating scales. Adverse events were recorded throughout the study.
At all time points, CaHA was found to be more effective than NASHA. At 12 months, 79% of CaHA folds were still improved or better versus 43% of NASHA folds (p<.0001). In addition, 30% less total CaHA volume was required compared to NASHA. Evaluators assessed CaHA as superior in 47% of patients and inferior in only 5% (p<.0001). Blinded evaluators and patients preferred CaHA two to one (p<.05). Both products were safe and well tolerated.
CaHA was found to be significantly more effective than NASHA. At all time points, CaHA demonstrated longer lasting results and greater improvement than NASHA.
With the baby boomer generation firmly ensconced in middle age and the ubiquity of botulinum toxin type A, nonsurgical facial rejuvenation is becoming increasingly prevalent. As this generation continues to age, products with greater therapeutic power to correct aging changes will be in growing demand.
A multicenter, double-blind, randomized, within-subject, controlled study was conducted comparing Juvéderm Ultra Plus hyaluronic acid filler with bovine collagen. A subset of subjects classified as having treatment for severe nasolabial folds is presented in this article. Subjects received Juvéderm Ultra Plus in one severe nasolabial fold and Zyplast collagen in the other nasolabial fold; up to two touch-up treatments were allowed at 2-week intervals. Nasolabial fold severity was evaluated every 4 weeks for 24 weeks using a five-point scale. Treatment site reactions and adverse events were also recorded. A complimentary treatment was offered at the end of the trial, with effectiveness evaluations just before retreatment and up to 48 weeks after repeated treatment for a subset of subjects.
Of the 87 subjects, most were female Caucasians, but all Fitzpatrick skin types were represented (36 percent types IV through VI). At 24 weeks, 96 percent of nasolabial folds treated with Juvéderm had maintained clinically significant correction, and 81 percent maintained the correction for 1 year or more. Results were similar for those subjects with follow-up through 48 weeks after repeated treatment. The median volume required for repeated treatment with Juvéderm was significantly less than that for initial treatment (0.7 ml versus 1.6 ml).
Juvéderm Ultra Plus provides correction of severe nasolabial folds through 1 year or more.
BACKGROUND At present, various hyaluronic acids are being used to rejuvenate facial skin. There is no comparative study of single cross-linked hyaluronic acid (SCHA) versus double cross-linked hyaluronic acid (DCHA). The objective of our study is to compare the effectiveness and complications of SCHA versus DCHA in the treatment of glabellar lines. METHODS Ten female patients were enrolled in this randomized, evaluator-blind study. One side (left vs. right) of each patient's glabellar lines was treated with SCHA and the other side was treated with DCHA. Two independent blinded observers reviewed the clinical photographs at 3, 6, 9, and 12 months after the treatment and assessed for degree of improvement as well as complications. RESULTS The two products were equally effective in producing an optimal cosmetic result, although at 6, 9, and 12 months posttreatment, a higher proportion of patients showed over 50% improvement with DCHA than with SCHA. At 12 months posttreatment, DCHA was considered superior in 70% of patients, whereas SCHA was superior in 10% of patients. CONCLUSIONS Both SCHA and DCHA are equally effective in producing an optimal cosmetic result. DCHA provides a more durable esthetic improvement when compared to SCHA in the treatment of glabellar lines.
Nonanimal-stabilized hyaluronic acid (NASHA) fillers are frequently used for facial soft tissue augmentation. Their long-term efficacy and the effects of different retreatment schedules are not well established.
This is an 18-month interim analysis of a 30-month study to evaluate the efficacy and persistence of NASHA 100,000 gel particles/mL filler with two different retreatment schedules.
This multicenter, randomized, evaluator-blinded study enrolled 75 patients with moderate to severe nasolabial folds. Patients were randomized to retreatment of one nasolabial fold at 4.5 months and the contralateral fold at 9 months after correction of both folds at the initial visit.
Wrinkle Severity Rating Scale scores improved significantly (p<.001) from baseline, with mean improvements ranging from 1.1 to 1.7 grades. Almost all patients (97%) responded satisfactorily, and the efficacy of the retreatment schedules did not differ significantly. Adverse events, primarily swelling and bruising, occurred in 33% of patients; none were serious.
The improvements seen after initial treatment with NASHA 100,000 gel particles/mL filler persisted for up to 18 months with one retreatment. The response was equivalent for retreatment at 4.5 and 9 months.
As physicians incorporate calcium hydroxylapatite (CaHA) into their aesthetic treatment regimens, the question has arisen of whether the addition of anesthetic agents to prefilled CaHA syringes might provide sufficient anesthetic prophylaxis to warrant reduction in conventional anesthetic pretreatment procedures.
Investigators sought to determine changes in the physical properties of CaHA induced by the addition of lidocaine and lidocaine with epinephrine into the prefilled CaHA syringe. The CaHA and gel carrier (CHM) were mixed with varying amounts of lidocaine and lidocaine with epinephrine to measure the number of passes back and forth for optimal homogeneity of lidocaine and CaHA in syringes, changes in viscosity, extrusion force, needle jam rates, elasticity, and pH.
Ten mixing passes appeared sufficient for homogeneity. Viscosities and extrusion forces of CHM/lidocaine blends decrease with increasing amount of lidocaine. Needle jams do not increase. The pH and elasticity of the CHM/lidocaine blend are essentially equivalent to those of CHM alone. Epinephrine added to lidocaine did not alter the results enough to reach statistical significance.
Addition of lidocaine to original CHM can be safely added without harmful changes in physical properties of the original soft tissue filler. Further studies are required to explore whether the addition of lidocaine to CHM alters patient discomfort, durability, and efficacy.